HistoryAssemble a list of drugs and rank themStop all drug candidatesTestAdminister - dose escalation or desensitization

Drug skin testing with invalidated reagents is not helpful if negative.

Reintroduction of a drug by serial dose escalations may be useful in idiosyncratic drug reactions of limited severity.

Re-challenge is strongly contraindicated in severe exfoliative dermatitis syndromes, and even with milder dermatoses that include mucosal membrane lesions.

History

History alone is often not sufficient for establishing drug sensitivity.

Fewer than 20% of patients with a history of drug allergy are really allergic to the offending drug. Diagnosis of sensitivity based on history alone is not sufficient.

Drug provocation tests are the gold standard for diagnosis of drug allergy.

Skin testing

Testing for drug-specific antibodies or lymphocytes is informative in theory, but no so much in practice.

Prick and intradermal skin testing for drug-specific IgE antibody have been usefully applied to β-lactam antibiotics and other drugs. Rate of false-negative tests is only well established for penicillins.

Penicillin minor determinants remain an ‘orphan drug’ in the USA and currently are accessible only under investigational protocols.

Allergic reactions observed in retreatment of history-positive, skin-test-negative patients have all been mild and self-limited; no life-threatening false-negative reactions have been reported.

More than 80% of history-positive patients will have negative penicillin skin tests.

Concentrations of 2–3 mg/mL of a cephalosporin are usually non-irritating, but each cephalosporin requires concurrent evaluation for its irritation potential in non-allergic subjects.

A positive cephalosporin skin test implies drug-specific IgE antibodies but a negative test does not exclude immediate hypersensitivity. Commercial cephalosporin skin test reagents are not available in the USA.

Specific IgE

In vitro test results have been compared with skin tests only in penicillin allergy.

Diagnostic sensitivity for penicilloyl-IgE is 65–85% compared with penicilloyl-polylysine skin tests and 32–50% compared with a combination of skin testing and provocational challenge.

Immunoassays for IgG, IgM, or IgA responses to drug allergens have not been useful.

IgG to the penicilloyl determinant occur in 50% of patients receiving PCN but this is not associated with drug allergy.

Lymphocyte proliferation

Lymphocyte activation tests using drugs as stimulants are often positive in drug-allergic subjects, but this indistinguishable from nonallergic patients.

Lymphocyte transformation test was positive in 78% of patients classified as highly likely to be drug allergic. Specificity was 85%; however, false-positive results were observed, especially with NSAIDs.